The present invention relates generally to the field of analytical separation and combining of samples and, more particularly, to a temporarily magnetizable biomagnetic particle collection, extraction and transfer device and a magnetic flux concentrator therefor.
Analytic and diagnostic procedures in the laboratory often require the transfer of a plurality of samples, simultaneously, from one array of liquid-containing wells to another. In order to transfer, add, collect or combine liquids, various multi-transferring systems have been devised. The most commonly used is a multi-pipette which collects liquid from an array of source wells for transfer to an array of target wells by application or release of application, respectively, of vacuum force. In operation, the pipette for collecting or releasing of liquid is connected to a single vacuum source provided to all the pipettes in the system so that all samples in the array of wells are collected and released at once.
In recent years, magnetic particles have been used for a variety of separation, purification, and isolation techniques in connection with chemical or biological molecules. In those techniques, a molecule is coupled to a magnetic particle capable of forming a specific binding with a molecule in a biological sample, which is to be isolated, purified or separated. The biological sample is then brought into contact with the magnetic particle and those biological molecules which bind to the magnetic particles are then isolated by application of a magnetic field.
Various devices have been developed to utilize such magnetic separation techniques in order to transfer the magnetic particles from one location to another. For example, U.S. Pat. No. 4,292,920 discloses a device including a single or multi-pin arrangement, corresponding to a micro-well arrangement, which is capable of insertion into the wells of a micro-plate to attract magnetic particles by magnetic force. In one embodiment, the pin is connected to an electromagnet, and by turning the electromagnet on and off the pin becomes magnetized, or non-magnetized, respectively.
U.S. Pat. No. 5,567,326 shows an apparatus and method for separating magnetically responsive particles from a nonmagnetic test medium in which they are suspended. The device comprises a plurality of nonmagnetic pins arranged in an array, and a magnet positioned normal to the array. Placing the magnet on the array of pins renders all the pins in the array magnetic thereby causing particles to be attracted to them. Removing the magnet causes the pins to become non-magnetic, and consequently the magnetic particles are released from the pins.
U.S. Pat. No. 6,409,925 to Gombinsky et al. discloses a device wherein each collecting pin can be independently controlled. Specifically, the disclosed magnetic rod design allows for a magnet disposed therein to be freely and independently movable up or down to thereby magnetically energize and de-energize the rod. Thus, each rod is independently magnetized regardless of the magnetization of the other rods.
Commonly owned U.S. Patent Application Publication No. 2006-0266130 discloses a transfer unit for transferring a sample, such as a biomagnetic particle sample, from a source vessel to a target vessel. The transfer unit includes a transfer device having a pin tip with a central bore terminating at a bottom wall, an actuating element, such as a magnet, movably disposed in the pin tip bore and an actuator rod for moving the actuating element. The actuator rod moves the actuating element between a first position adjacent the tip bottom wall and a second position away from the bottom wall. Movement of the actuating element causes a sample in proximity to the pin tip to be alternately collected and released from the pin tip.
The above described devices all have certain drawbacks. One drawback resides in the fact that the ends of the magnetic rods or pins must come into direct contact with the magnetic particles in the liquid sample to ensure a sufficiently strong magnetic field to collect the particles. To protect the magnet elements and/or pins from contaminants, plastic tips are provided over the ends of the pins, which must be loaded and unloaded between applications. Additionally, the tips must be extremely thin-walled (e.g., less than 20 micrometers) to permit the magnetic field to pass therethrough without diminishing in strength. Such thin-walled tips are difficult to manufacture and are expensive. Moreover, in most applications, rinsing and sterilization is required wherein the tips must be removed from the pins and subsequently replaced. Such thin-walled tips are difficult to handle and are not particularly durable to withstand rinsing and sterilization.
Another trend in the field is to reduce the overall size of the sample wells while simultaneously increasing the number of wells within an array. As a result, pins having smaller diameters must be utilized and these pins must be arranged in closer proximity to one another. Placing pins in close proximity to one another raises the challenge of minimizing the effects of magnetic fields between adjacent pins so that the magnetic field applied in one sample well will not affect the magnetic particles in a neighboring well. Also, reducing the diameter of the pins means using a smaller magnetic element having a weaker magnetic strength.
Accordingly, it would be desirable to provide a tip to a biomagnetic particle transfer device which is inexpensive to manufacture, yet durable enough to withstand repeated use with washing and sterilization between each use. It would be further desirable to provide such a tip which enhances the magnetic strength of a magnetic pin, particularly in compact arrangements.